Methods and paradigms are proposed for maintaining rats for extended periods of time (20-25% of mature life span) in order to attempt to both retard and/or accelerate rate of development of brain aging pathology using long-term hormonal-pharmacological manipulations. Animals would be maintained behind an air barrier system to prevent airborne infections. For 7-9 months, rats will be given specific hormonal and pharmacological agents for which there are some data available suggesting a possible relationship to brain aging mechanisms. The animals will be tested for learning, motivation and sensory-motor functions. The brain of the animals will then be morphometrically analyzed in detail at the light and electron microscopic levels. Attempts will be made to determine if the electron microscopic brain changes induced by hormonal treatments are similar in detailed pattern and topography to those seen during normal aging.